Mechanisms by which fibrinogen synthesis is regulated will be investigated. The effects of purified species of fibrinogen-fibrin degradation products and their asialo-derivatives upon production of fibrinogen, in vitro, will be studied. The carbohydrate content and the primary structure of the carbohydrate associated with fibrinogen will be identified. Thrombopoietin, obtained from the plasma of thrombocytopenic rabbits, will be further purified using ammonium sulfate precipitation and lectin-agarose as the initial chromatographic step. Attempts will be made to utilize in vitro cultures of hematopoietic cells for the direct study of the effects of thrombopoietin on megakaryocyte numbers, size, and DNA content. The components of amebocyte lysate that react with bacterial endotoxin will be identified and the nature of the reaction(s) characterized. The presence of bacterial endotoxin in the cerebrospinal fluids of patients with various forms of meningitis will be sought and correlated with other clinical and laboratory measurements. Improved methods for the transfusion of patients with inherited disorders of blood coagulation will be sought.